Joint International Research Laboratory of Glycobiology and Medicinal Chemistry College of Life Science Northwest University Xi'an P.R. China.
Department of Breast Surgery The First Affiliated Hospital of Xi'an Jiaotong University Xi'an P.R. China.
J Extracell Vesicles. 2020 Oct;10(1):e12005. doi: 10.1002/jev2.12005. Epub 2020 Oct 30.
Small extracellular vesicles (sEVs) are enriched in glycoconjugates and display specific glycosignatures. Aberrant expression of surface glycoconjugates is closely correlated with cancer progression and metastasis. The essential functions of glycoconjugates in sEVs are poorly understood. In this study, we observed significantly reduced levels of bisecting GlcNAc in breast cancer. Introduction of bisecting GlcNAc into breast cancer cells altered the bisecting GlcNAc status on sEVs, and sEVs with diverse bisecting GlcNAc showed differing functions on recipient cells. Carcinogenesis and metastasis of recipient cells were enhanced by sEVs with low bisecting GlcNAc, and the pro-metastatic functions of sEVs was diminished by high bisecting GlcNAc modification. We further identified vesicular integrin β1 as a target protein bearing bisecting GlcNAc. Metastasis of recipient cells was strongly suppressed by high bisecting GlcNAc levels on vesicular β1. Our findings demonstrate the important roles of glycoconjugates on sEVs. Modification of sEV glycosylation may contribute to development of novel targets in breast cancer therapy.
小细胞外囊泡（sEVs）富含糖缀合物，并显示出特定的糖基化特征。表面糖缀合物的异常表达与癌症的进展和转移密切相关。糖缀合物在 sEVs 中的基本功能尚未得到充分了解。在本研究中，我们观察到乳腺癌中双分支 GlcNAc 的水平显著降低。在乳腺癌细胞中引入双分支 GlcNAc 会改变 sEV 上的双分支 GlcNAc 状态，并且具有不同双分支 GlcNAc 的 sEV 对受体细胞具有不同的功能。具有低双分支 GlcNAc 的 sEV 增强了受体细胞的癌变和转移，而高双分支 GlcNAc 修饰则减弱了 sEV 的促转移功能。我们进一步鉴定了带有双分支 GlcNAc 的囊泡整合素 β1 作为靶蛋白。受体细胞的转移被囊泡 β1 上高双分支 GlcNAc 水平强烈抑制。我们的研究结果表明了糖缀合物在 sEVs 中的重要作用。sEV 糖基化的修饰可能有助于开发乳腺癌治疗的新靶点。
